Oligonucleotide- based therapeutics and in vivo functional genomics is a cutting-edge area of research and development. The discovery of RNAi by University of Massachusetts Medical School Professor Craig Mello received the Nobel Prize in 2006. RNAi and Antisense-based drugs have proven clinical efficacy and are believed to become a novel major class of therapeutic modalities. At the University of Massachusetts Medical School (UMMS), there are multiple groups whose research has reached the stage at which functional analysis of novel and advanced oligonucleotides in animal models and preclinical development is necessary. These types of studies require access to mid-scale, uniquely chemically modified oligonucleotides that have limited commercial availability and are outside the reach of academic investigators. A Shared Instrumentation Grant will allow us to purchase the equipment to support mid scale synthesis, purification and quality control of chemically modified RNA that will enable ongoing and planned animal models and preclinical studies for research supported by 11 NIH grants and multiple grants from private foundations. Specifically, we are requesting funds to purchase a GE AKTA Pilot 10 RNA synthesizer, 218 Prep HPLC and 6530 QTOF LC- MS. The acquisition of this state-of-the-art RNA synthesis capability will propel our research and translational programs and enable the development of novel RNA-based therapies, specifically for treatment of Preeclampsia, ALS (amyotrophic lateral sclerosis), HSAN (hereditary sensory and autonomic neuropathy), Huntington, IBD (inflammatory bowel disease) and other diseases.